Oxidation of fatty acids occurs. Fatty acid oxidation and energy release

Fatty acid oxidation is the process of breakdown of fatty acids, which occurs with the release of energy. In this article you will learn why this chemical reaction is extremely important for our body.

Fatty acids are formed during the breakdown of fats. Such fats can accumulate in the body and be used later for energy. Fatty acids are necessary for the human body because they participate in the transport of oxygen through the circulatory system, strengthen cell membranes, and also ensure the coordinated functioning of all organs and tissues. Fatty acids lower cholesterol by preventing the formation of plaque in the arteries and lowering triglyceride levels. Fatty acids also prevent the appearance of wrinkles, helping to keep the skin healthy and elastic.

There are three types of fatty acids: omega-3, omega-6 and omega-9. Omega-3 and omega-6 are called essential because they help regulate blood lipid levels. Blood clotting and blood pressure depend on this. In addition, essential fatty acids stimulate the immune system.

Fatty acid oxidation and energy release

The main source of energy for the body is glucose. If the supply of glucose is depleted, the process of breaking down the reserves of fatty acids begins. It proceeds with the release of energy. The same thing happens when carbohydrates are broken down, but fatty acids release more energy per carbon atom.

It is important for the body to break down stored fats because sometimes the body needs energy at that moment. when there is no suitable source of food to process.

Fatty acid oxidation disorder

Some people's bodies are unable to break down stored fats due to malfunctions or lack of certain enzymes. This is often due to genetic factors. This means that, lacking energy and lacking a food source, the body cannot use fats. As a result, fatty acids are not broken down and accumulate in the blood, which means that fats continue to be deposited. This can lead to serious health problems.

The most common cause of disturbances in the oxidation of fatty acids is carnitine deficiency. Carnitine is an amino acid that transports fatty acids into the mitochondria, where they are broken down to release energy. Carnitine also regulates metabolism, preventing low blood sugar levels and helping to remove cellular waste that can lead to toxicity.

How to increase the amount of fatty acids in your diet

Fatty acids are found in fish and some plants. Omega-3 and omega-6 fatty acids are not synthesized in our bodies, so they must be obtained from food or taken in the form of dietary supplements. Sources of fatty acids include salmon, tuna, mackerel, flax seeds, soybean and safflower oils. Fish oil capsules are commonly taken as dietary supplements.

Article prepared: Olga Pozikhovskaya

All multistage oxidation reactions are accelerated by specific enzymes. β-Oxidation of higher fatty acids is a universal biochemical process that occurs in all living organisms. In mammals, this process occurs in many tissues, most notably the liver, kidneys, and heart. Unsaturated higher fatty acids (oleic, linoleic, linolenic, etc.) are preliminarily reduced to saturated acids.

In addition to β-oxidation, which is the main process of fatty acid degradation in animals and humans, there are also α-oxidation and ω-oxidation. α-Oxidation occurs in both plants and animals, however, the entire process occurs in peroxisomes. ω-Oxidation is less common among animals (vertebrates), occurring mainly in plants. The process of ω-oxidation occurs in the endoplasmic reticulum (ER).

β-Oxidation was discovered in 1904 by a German chemist ( Franz Knoop) in experiments with feeding dogs with various fatty acids, in which one hydrogen atom on the terminal ω-C carbon atom of the methyl group -CH 3 was replaced by a phenyl radical -C 6 H 5 .

Franz Knoop suggested that the oxidation of a fatty acid molecule in body tissues occurs in the β-position. As a result, two-carbon fragments are sequentially split off from the fatty acid molecule on the side of the carboxyl group.

The theory of β-oxidation of fatty acids, proposed by F. Knoop, largely served as the basis for modern ideas about the mechanism of fatty acid oxidation.

Fatty acids that are formed in the cell by hydrolysis of triacylglycerides or that enter it from the blood must be activated, since they themselves are metabolic inert substances, and as a result cannot be subject to biochemical reactions, including oxidation. The process of their activation occurs in the cytoplasm with the participation of ATP, coenzyme A (HS-CoA) and Mg 2+ ions. The reaction is catalyzed by the enzyme long chain fatty acid acyl-CoA synthetase ( Long-chain-fatty-acid-CoA ligase, KF), the process is endergonic, that is, it occurs through the use of the energy of hydrolysis of the ATP molecule:

acyl-CoA synthetases are found both in the cytoplasm and in the mitochondrial matrix. These enzymes differ in their specificity for fatty acids with different hydrocarbon chain lengths. Fatty acids with short and medium chain length (from 4 to 12 carbon atoms) can penetrate into the mitochondrial matrix by diffusion. Activation of these fatty acids occurs in the mitochondrial matrix.

Long-chain fatty acids, which predominate in the human body (12 to 20 carbon atoms), are activated by acyl-CoA synthetases located on the outer side of the mitochondrial outer membrane.

The pyrophosphate released during the reaction is hydrolyzed by the enzyme pyrophosphatase (CP):

In this case, the reaction equilibrium shifts towards the formation of acyl-CoA.

Since the process of activation of fatty acids occurs in the cytoplasm, then the transport of acyl-CoA through the membrane into the mitochondria is necessary.

Transport of long chain fatty acids across the dense mitochondrial membrane is mediated by carnitine. In the outer membrane of mitochondria there is the enzyme carnitine acyltransferase I (carnitine palmitoyltransferase I, CPT1, CP), which catalyzes the reaction with the formation of acylcarnitine (the acyl group is transferred from the sulfur atom of CoA to the hydroxyl group of carnitine to form acylcarnitine (carnitine-COR)), which diffuses through the inner membrane mitochondrial membrane:

The resulting acylcarnitine passes through the intermembrane space to the outside of the inner membrane and is transported by the enzyme carnitine acylcarnitine translocase (CACT).

After the passage of acylcarnitine (carnitine-COR) through the mitochondrial membrane, a reverse reaction occurs - the cleavage of acylcarnitine with the participation of CoA-SH and the enzyme mitochondrial carnitine acyl-CoA transferase or carnitine acyltransferase II (carnitine palmitoyltransferase II, CPT2, CP):

Thus, acyl-CoA becomes available to β-oxidation enzymes. Free carnitine is returned to the cytoplasmic side of the inner mitochondrial membrane by the same translocase.

The process of transmembrane transfer of fatty acids can be inhibited by malonyl-CoA.

In the mitochondrial matrix, fatty acids are oxidized in the Knoopp-Linene cycle. It involves four enzymes that act sequentially on acyl-CoA. The final metabolite of this cycle is acetyl-CoA. The process itself consists of four reactions.

The resulting acetyl-CoA undergoes oxidation in the Krebs cycle, and acyl-CoA, shortened by two carbon atoms, again repeatedly goes through the entire β-oxidation path until the formation of butyryl-CoA (4-carbon compound), which in turn is oxidized to 2 molecules acetyl-CoA. FADH 2 and NADH H go directly into the respiratory chain.

For complete degradation of a long-chain fatty acid, the cycle must be repeated many times, for example, eight cycles are required for stearyl-CoA (C 17 H 35 CO ~ SCoA).

As a result of the oxidation of fatty acids with an odd number of carbon atoms, not only acetyl-CoA, FAD H 2 and NADH are formed, but also one molecule of propionyl-CoA (C 2 H 5 -CO~SCoA).

When oxidizing fatty acids that have two (-C=C-C-C=C-) or more unsaturated bonds, another additional enzyme, β-hydroxyacyl-CoA epimerase (HF), is required.

The rate of oxidation of unsaturated fatty acids is much higher than that of saturated fatty acids, which is due to the presence of double bonds. For example, if we take the rate of oxidation of saturated stearic acid as a standard, then the rate of oxidation of oleic acid is 11, linoleic is 114, linolenic is 170, and arachidonic acid is almost 200 times higher than stearic acid.

As a result of the transfer of electrons along the ETC from FAD H 2 and NADH, 5 ATP molecules are synthesized (2 from FADH 2, and 3 from NADH). In the case of palmitic acid oxidation, 7 cycles of β-oxidation (16/2-1=7) occur, which leads to the formation of 5 7 = 35 ATP molecules. In the process of β-oxidation of palmitic acid, n molecules of acetyl-CoA, each of which, with complete combustion in the tricarboxylic acid cycle, gives 12 molecules of ATP, and 8 molecules will give 12 8 = 96 molecules of ATP.

Thus, in total, with complete oxidation of palmitic acid, 35 + 96 = 131 ATP molecules are formed. However, taking into account one molecule of ATP, which is hydrolyzed to AMP, that is, 2 high-energy bonds or two ATP are spent, at the very beginning for the activation process (formation of palmitoyl-CoA), the total energy yield for the complete oxidation of one molecule of palmitic acid under the conditions of an animal organism will be 131 -2=129 molecules.

The overall equation for the oxidation of palmitic acid is as follows:

The formula for calculating the total amount of ATP that is generated as a result of the β-oxidation process is:

Energy calculations of β-oxidation for some fatty acids are presented in table form.

In addition to β-oxidation of fatty acids that occurs in mitochondria, there is also extramitochondrial oxidation. Fatty acids with a longer chain length (from C20) cannot be oxidized in mitochondria due to the presence of a dense double membrane, which will prevent the process of transporting them through the intermembrane space. Therefore, the oxidation of long-chain fatty acids (C 20 -C 22 and more) occurs in peroxisomes. In peroxisomes, the process of β-oxidation of fatty acids occurs in a modified form. The oxidation products in this case are acetyl-CoA, octanoyl-CoA and hydrogen peroxide H 2 O 2. Acetyl-CoA is formed in a step catalyzed by FAD-dependent dehydrogenase. Peroxisomal enzymes do not attack short-chain fatty acids, and the β-oxidation process stops when octanoyl-CoA is formed.

This process is not associated with oxidative phosphorylation and ATP generation, and therefore octanoyl-CoA and acetyl-CoA are transferred from CoA to carnitine and sent to mitochondria, where they are oxidized to form ATP.

Activation of peroxisomal β-oxidation occurs when there is an excess content of fatty acids in the food consumed, starting with C20, as well as when taking lipid-lowering drugs.

The rate of β-oxidation also depends on the activity of the enzyme carnitine palmitoyltransferase I (CPTI). In the liver, this enzyme is inhibited by malonyl-CoA, a substance formed during the biosynthesis of fatty acids.

In muscle, carnitine palmitoyltransferase I (CPTI) is also inhibited by malonyl-CoA. Although muscle tissue does not synthesize fatty acids, it does contain an acetyl-CoA carboxylase isoenzyme that synthesizes malonyl-CoA to regulate β-oxidation. This isoenzyme is phosphorylated by protein kinase A, which is activated in cells under the influence of adrenaline, and by AMP-dependent protein kinase and thus inhibits it; the concentration of malonyl-CoA decreases. As a result, during physical work, when AMP appears in the cell, β-oxidation is activated under the influence of adrenaline, however, its speed also depends on the availability of oxygen. Therefore, β-oxidation becomes a source of energy for muscles only 10-20 minutes after the start of physical activity (so-called aerobic exercise), when the flow of oxygen to the tissues increases.

Defects in the carnitine transport system manifest themselves in fermentopathy and carnitine deficiency in the human body.

The most common deficiency conditions associated with the loss of carnitine during certain body conditions are:

Signs and symptoms of carnitine deficiency include attacks of hypoglycemia resulting from decreased gluconeogenesis as a result of impaired β-oxidation of fatty acids, decreased formation of ketone bodies accompanied by increased levels of free fatty acids (FFA) in the blood plasma, muscle weakness (myasthenia gravis), and also lipid accumulation.

In mitochondria there are 3 types of acyl-CoA dehydrogenases that oxidize fatty acids with long, medium or short chain radicals. Fatty acids can be sequentially oxidized by these enzymes as the radical is shortened during β-oxidation. Genetic defect (DF) - MCADD(abbreviated from M edium- c hain a cyl-CoA d ehydrogenase d eficiency) is the most common compared to other hereditary diseases - 1:15,000. Frequency of the defective gene ACADM, encoding acyl-CoA dehydrogenases of medium-chain fatty acids, among the European population - 1:40. It is an autosomal recessive disorder resulting from a substitution of the T nucleotide (.

Dicarboxylic aciduria is a disease associated with increased excretion of C 6 -C 10 dicarboxylic acids and the resulting hypoglycemia, however, not associated with an increase in the content of ketone bodies. The cause of this disease is MCADD. In this case, β-oxidation is disrupted and ω-oxidation of long-chain fatty acids is enhanced, which are shortened to medium-chain dicarboxylic acids, which are excreted from the body.

Zellweger syndrome or cerebrohepatorenal syndrome, a rare hereditary disease described by American pediatrician Hans Zellweger (eng. H.U. Zellweger), which manifests itself in the absence of peroxisomes in all tissues of the body. As a result, polyenoic acids (C 26 -C 38), which are long-chain fatty acids, accumulate in the body, especially in the brain. The estimated incidence of peroxisome biogenesis disorders of the Zellweger syndrome spectrum is 1:50,000 newborns in the United States and 1:500,000 newborns in Japan. The syndrome is characterized by: prenatal growth retardation; muscle hypotension; difficulty sucking; areflexia; dolichocephaly; high forehead; round flat face; puffy eyelids; hypertelorism; Mongoloid eye shape; cataract; pigmentary retinopathy or optic nerve dysplasia; iris coloboma; low-set ears; micrognathia; cleft palate; lateral or medial curvature of the fingers; liver damage (hepatomegaly (increase in liver volume), dysgynesia of the intrahepatic ducts, cirrhosis of the liver); polycystic kidney disease; often - severe, incompatible with life, lung anomalies and heart defects; delayed psychomotor development; convulsions; persistent jaundice. Pathomorphological examination reveals a delay in myelination of neurons; accumulation of lipids in astrocytes; the content of plasmogens is reduced in the liver, kidneys and brain; in liver cells and other tissues of the body the number of peroxisomes is reduced, most peroxisomal enzymes are inactive. The activity of transaminases in the blood is increased and persistent hyperbilirubinemia is noted. In the presence of hypoglycine, accumulation occurs mainly of butyryl-CoA, which is hydrolyzed to free butyric acid (butyrate). Butyric acid in excess enters

occurs in the liver, kidneys, skeletal and cardiac muscles, and adipose tissue. In brain tissue, the rate of fatty acid oxidation is very low; The main source of energy in brain tissue is glucose.

oxidation of the fatty acid molecule in body tissues occurs in the β-position. As a result, two-carbon fragments are sequentially split off from the fatty acid molecule on the side of the carboxyl group.

Fatty acids, which are part of the natural fats of animals and plants, have an even number of carbon atoms. Any such acid from which a pair of carbon atoms is eliminated eventually passes through the butyric acid stage. After another β-oxidation, butyric acid becomes acetoacetic acid. The latter is then hydrolyzed to two molecules of acetic acid.

The delivery of fatty acids to the site of their oxidation - to the mitochondria - occurs in a complex way: with the participation of albumin, the fatty acid is transported into the cell; with the participation of special proteins (fatty acid binding proteins, FABP) – transport within the cytosol; with the participation of carnitine - transport of fatty acids from the cytosol to the mitochondria.

The process of fatty acid oxidation consists of the following main stages.

Activationfatty acids. Free fatty acid, regardless of the length of the hydrocarbon chain, is metabolically inert and cannot undergo any biochemical transformations, including oxidation, until it is activated. Activation of the fatty acid occurs on the outer surface of the mitochondrial membrane with the participation of ATP, coenzyme A (HS-KoA) and Mg 2+ ions. The reaction is catalyzed by the enzyme acyl-CoA synthetase:

As a result of the reaction, acyl-CoA is formed, which is the active form of the fatty acid.

It is believed that the activation of fatty acid occurs in 2 stages. First, the fatty acid reacts with ATP to form acyladenylate, which is an ester of the fatty acid and AMP. Next, the sulfhydryl group of CoA acts on the acyladenylate tightly bound to the enzyme to form acyl-CoA and AMP.

Transportfatty acidsinside mitochondria. The coenzyme form of the fatty acid, just like free fatty acids, does not have the ability to penetrate into the mitochondria, where, in fact, their oxidation occurs. Carnitine serves as a carrier of activated long-chain fatty acids across the inner mitochondrial membrane. The acyl group is transferred from the sulfur atom of CoA to the hydroxyl group of carnitine to form acylcarnitine, which diffuses across the inner mitochondrial membrane:

The reaction occurs with the participation of a specific cytoplasmic enzyme, carnitine acyltransferase. Already on the side of the membrane that faces the matrix, the acyl group is transferred back to CoA, which is thermodynamically favorable, since the O-acyl bond in carnitine has a high group transfer potential. In other words, after acylcarnitine passes through the mitochondrial membrane, a reverse reaction occurs - the cleavage of acylcarnitine with the participation of HS-CoA and mitochondrial carnitine acyltransferase:

Intramitochondrialfatty acid oxidation. The process of fatty acid oxidation in cell mitochondria includes several sequential enzymatic reactions.

First stage of dehydrogenation. Acyl-CoA in mitochondria first undergoes enzymatic dehydrogenation, and acyl-CoA loses 2 hydrogen atoms in the α- and β-positions, turning into the CoA ester of an unsaturated acid. Thus, the first reaction in each cycle of acyl-CoA breakdown is its oxidation by acyl-CoA dehydrogenase, leading to the formation of enoyl-CoA with a double bond between C-2 and C-3:

There are several FAD-containing acyl-CoA dehydrogenases, each of which has specificity for acyl-CoA of a certain carbon chain length.

Stagehydration. Unsaturated acyl-CoA (enoyl-CoA), with the participation of the enzyme enoyl-CoA hydratase, attaches a water molecule. As a result, β-hydroxyacyl-CoA (or 3-hydroxyacyl-CoA) is formed:

Note that the hydration of enoyl-CoA is stereospecific, like the hydration of fumarate and aconitate (see p. 348). As a result of hydration of the trans-Δ 2 double bond, only the L-isomer of 3-hydroxyacyl-CoA is formed.

Second stagedehydrogenation. The resulting β-hydroxyacyl-CoA (3-hydroxyacyl-CoA) is then dehydrogenated. This reaction is catalyzed by NAD+-dependent dehydrogenases:

Thiolasereaction. During the previous reactions, the methylene group at C-3 was oxidized into an oxo group. The thiolase reaction is the cleavage of 3-oxoacyl-CoA using the thiol group of the second CoA molecule. As a result, an acyl-CoA shortened by two carbon atoms and a two-carbon fragment in the form of acetyl-CoA are formed. This reaction is catalyzed by acetyl-CoA acyltransferase (β-ketothiolase):

The resulting acetyl-CoA undergoes oxidation in the tricarboxylic acid cycle, and acyl-CoA, shortened by two carbon atoms, again repeatedly goes through the entire β-oxidation path until the formation of butyryl-CoA (4-carbon compound), which in turn is oxidized up to 2 acetyl-CoA molecules

During one cycle of β-oxidation, 1 molecule of acetyl-CoA is formed, the oxidation of which in the citrate cycle ensures the synthesis 12 mol ATP. In addition, it forms 1 mol FADH 2 and 1 mol NADH+H, during the oxidation of which in the respiratory chain it is synthesized, respectively 2 and 3 moles of ATP (5 in total).

Thus, during the oxidation of, for example, palmitic acid (C16), 7 β-oxidation cycles, resulting in the formation of 8 mol of acetyl-CoA, 7 mol of FADH 2 and 7 mol of NADH+H. Therefore, the ATP output is 35 molecules as a result of β-oxidation and 96 ATP resulting from the citrate cycle, which corresponds to the total 131 ATP molecules.

2.1. Oxidation of fatty acids in cells

Higher fatty acids can be oxidized in cells in three ways:

a) by a-oxidation,

b) by b-oxidation,

c) by w-oxidation.

The processes of a- and w-oxidation of higher fatty acids occur in cell microsomes with the participation of monooxygenase enzymes and play a mainly plastic function - during these processes, the synthesis of hydroxy acids, keto acids and acids with an odd number of carbon atoms necessary for cells occurs. Thus, during a-oxidation, a fatty acid can be shortened by one carbon atom, thus turning into an acid with an odd number of “C” atoms, in accordance with the given scheme:

2.1.1. b-Oxidation of higher fatty acids The main method of oxidation of higher fatty acids, at least in relation to the total amount of compounds of this class oxidized in the cell, is the process of b-oxidation, discovered by Knoop back in 1904. This process can be defined as the process of stepwise oxidative breakdown of higher fatty acids. fatty acids, during which there is a sequential cleavage of two-carbon fragments in the form of acetyl-CoA from the carboxyl group of the activated higher fatty acid molecule.

Higher fatty acids entering the cell are activated and converted into acyl-CoA (R-CO-SKoA), and the activation of fatty acids occurs in the cytosol. The process of b-oxidation of fatty acids occurs in the mitochondrial matrix. At the same time, the inner membrane of mitochondria is impermeable to acyl-CoA, which raises the question of the mechanism of transport of acyl residues from the cytosol to the mitochondrial matrix.

Acyl residues are transported across the inner mitochondrial membrane using a special carrier, which is carnitine (CN):

In the cytosol, with the help of the enzyme external acylCoA:carnitine acyltransferase (E1 in the diagram below), the higher fatty acid residue is transferred from coenzyme A to carnitine to form acylcarnitine:

Acylcarnitinine, with the participation of a special carnitine-acylcarnitine-translocase system, passes through the membrane into the mitochondria and in the matrix, with the help of the enzyme internal acyl-CoA: carnitine acyltransferase (E2), the acyl residue is transferred from carnitine to intramitochondrial coenzyme A. As a result, an activated residue appears in the mitochondrial matrix fatty acid in the form of acyl-CoA; the released carnitine, using the same translocase, passes through the mitochondrial membrane into the cytosol, where it can be included in a new transport cycle. Carnitine acylcarnitine translocase, built into the inner membrane of mitochondria, transfers an acylcarnitine molecule into the mitochondrion in exchange for a carnitine molecule removed from the mitochondrion.

Activated fatty acid in the mitochondrial matrix undergoes stepwise cyclic oxidation according to the following scheme:

As a result of one cycle of b-oxidation, the fatty acid radical is shortened by 2 carbon atoms, and the cleaved fragment is released as acetyl-CoA. Summary cycle equation:

During one cycle of b-oxidation, for example, during the conversion of stearoyl-CoA to palmitoyl-CoA with the formation of acetyl-CoA, 91 kcal/mol of free energy is released, but the bulk of this energy accumulates in the form of energy from reduced coenzymes, and energy loss in the form heat amounts to only about 8 kcal/mol.

The resulting acetyl-CoA can enter the Krebs cycle, where it will be oxidized to final products, or it can be used for other cell needs, for example, for the synthesis of cholesterol. Acyl-CoA, shortened by 2 carbon atoms, enters a new b-oxidation cycle. As a result of several successive cycles of oxidation, the entire carbon chain of the activated fatty acid is cleaved into "n" acetyl-CoA molecules, the value of "n" being determined by the number of carbon atoms in the original fatty acid.

The energy effect of one b-oxidation cycle can be assessed based on the fact that during the cycle 1 molecule of FADH2 and 1 molecule of NADH + H are formed. When they enter the chain of respiratory enzymes, 5 ATP molecules (2 + 3) will be synthesized. If the resulting acetyl-CoA is oxidized in the Krebs cycle, the cell will receive 12 more ATP molecules.

For stearic acid, the overall equation for its b-oxidation has the form:

Calculations show that during the oxidation of stearic acid in the cell, 148 ATP molecules will be synthesized. When calculating the energy balance of oxidation, it is necessary to exclude from this amount 2 macroergic equivalents expended during the activation of a fatty acid (during activation, ATP is broken down into AMP and 2 H3PO4). Thus, when stearic acid is oxidized, the cell will receive 146 ATP molecules.

For comparison: during the oxidation of 3 glucose molecules, which also contain 18 carbon atoms, the cell receives only 114 ATP molecules, i.e. Higher fatty acids are more beneficial energy fuel for cells compared to monosaccharides. Apparently, this circumstance is one of the main reasons that the body's energy reserves are presented predominantly in the form of triacylglycerols rather than glycogen.

The total amount of free energy released during the oxidation of 1 mole of stearic acid is about 2632 kcal, of which about 1100 kcal is accumulated in the form of energy from high-energy bonds of synthesized ATP molecules. Thus, approximately 40% of the total free energy released is accumulated.

The rate of b-oxidation of higher fatty acids is determined, firstly, by the concentration of fatty acids in the cell and, secondly, by the activity of external acyl-CoA:carnitine acyltransferase. The activity of the enzyme is inhibited by malonyl-CoA. We will dwell on the meaning of the last regulatory mechanism a little later, when we discuss the coordination of the processes of oxidation and synthesis of fatty acids in the cell.

Orange tonsils and accumulation of cholesterol esters in other reticuloendothelial tissues. The pathology is associated with accelerated catabolism of apo A-I. Digestion and absorption of lipids. Bile. Meaning. At the dawn of the formation of the modern doctrine of the exocrine function of the liver, when natural scientists had only the first...

The dynamics of chemical transformations occurring in cells is studied by biological chemistry. The task of physiology is to determine the total expenditure of substances and energy by the body and how they should be replenished with the help of adequate nutrition. Energy metabolism serves as an indicator of the general condition and physiological activity of the body. A unit of energy measurement commonly used in biology and...

Acids that are classified as essential fatty acids (linoleic, linolenic, arachidonic), which are not synthesized in humans and animals. With fats, a complex of biologically active substances enters the body: phospholipids, sterols. Triacylglycerols – their main function is lipid storage. They are found in the cytosol in the form of fine emulsified oily droplets. Complex fats:...

... α,d – glucose glucose – 6 – phosphate With the formation of glucose – 6 – phosphate, the paths of glycolysis and glycogenolysis coincide. Glucose-6-phosphate occupies a key place in carbohydrate metabolism. It enters the following metabolic pathways: glucose - 6 - phosphate glucose + H3PO4 fructose - 6 - phosphate pentose breakdown pathway (enters the blood, etc. ...

And the respiratory chain, to convert the energy contained in fatty acids into the energy of ATP bonds.

Fatty acid oxidation (β-oxidation)

Elementary diagram of β-oxidation.

This path is called β-oxidation, since the 3rd carbon atom of the fatty acid (β-position) is oxidized into a carboxyl group, and at the same time the acetyl group, including C 1 and C 2 of the original fatty acid, is cleaved from the acid.

β-oxidation reactions occur in the mitochondria of most cells in the body (except nerve cells). For oxidation, fatty acids are used that enter the cytosol from the blood or appear during lipolysis of their own intracellular TAG. The overall equation for the oxidation of palmitic acid is as follows:

Palmitoyl-SCoA + 7FAD + 7NAD + + 7H 2 O + 7HS-KoA → 8Acetyl-SCoA + 7FADH 2 + 7NADH

Stages of fatty acid oxidation

Fatty acid activation reaction.

1. Before penetrating the mitochondrial matrix and being oxidized, the fatty acid must be activated in the cytosol. This is accomplished by the addition of coenzyme A to it to form acyl-S-CoA. Acyl-S-CoA is a high-energy compound. Irreversibility of the reaction is achieved by hydrolysis of diphosphate into two molecules of phosphoric acid.

Carnitine-dependent transport of fatty acids into the mitochondria.

2. Acyl-S-CoA is not able to pass through the mitochondrial membrane, so there is a way to transport it in combination with the vitamin-like substance carnitine. The outer membrane of mitochondria contains the enzyme carnitine acyltransferase I.

Carnitine is synthesized in the liver and kidneys and then transported to other organs. In the prenatal period and in the first years of life, the importance of carnitine for the body is extremely great. The energy supply to the nervous system of the child’s body and, in particular, the brain is carried out through two parallel processes: carnitine-dependent oxidation of fatty acids and aerobic oxidation of glucose. Carnitine is necessary for the growth of the brain and spinal cord, for the interaction of all parts of the nervous system responsible for movement and muscle interaction. There are studies linking cerebral palsy and the phenomenon of “death in the cradle” to carnitine deficiency.

3. After binding to carnitine, the fatty acid is transported across the membrane by translocase. Here, on the inner side of the membrane, the enzyme carnitine acyltransferase II again forms acyl-S-CoA, which enters the β-oxidation pathway.

Sequence of reactions of β-oxidation of fatty acids.

4. The process of β-oxidation itself consists of 4 reactions, repeated cyclically. They sequentially undergo oxidation (acyl-SCoA dehydrogenase), hydration (enoyl-SCoA hydratase) and again oxidation of the 3rd carbon atom (hydroxyacyl-SCoA dehydrogenase). In the last, transferase reaction, acetyl-SCoA is cleaved from the fatty acid. HS-CoA is added to the remaining (shortened by two carbons) fatty acid, and it returns to the first reaction. This is repeated until the last cycle produces two acetyl-SCoAs.

Calculation of the energy balance of β-oxidation

When calculating the amount of ATP formed during β-oxidation of fatty acids, it is necessary to take into account:

• the amount of acetyl-SCoA formed is determined by the usual division of the number of carbon atoms in the fatty acid by 2;
• number of β-oxidation cycles. The number of β-oxidation cycles is easy to determine based on the concept of a fatty acid as a chain of two-carbon units. The number of breaks between units corresponds to the number of β-oxidation cycles. The same value can be calculated using the formula (n/2 −1), where n is the number of carbon atoms in the acid;
• number of double bonds in a fatty acid. In the first β-oxidation reaction, a double bond is formed with the participation of FAD. If a double bond is already present in the fatty acid, then there is no need for this reaction and FADH 2 is not formed. The number of unformed FADN 2 corresponds to the number of double bonds. The remaining reactions of the cycle proceed without changes;
• the amount of ATP energy spent on activation (always corresponds to two high-energy bonds).

Example. Oxidation of palmitic acid

• Since there are 16 carbon atoms, β-oxidation produces 8 molecules of acetyl-SCoA. The latter enters the TCA cycle; when it is oxidized in one turn of the cycle, 3 molecules of NADH, 1 molecule of FADH 2 and 1 molecule of GTP are formed, which is equivalent to 12 molecules of ATP (see also Methods of obtaining energy in the cell). So, 8 molecules of acetyl-S-CoA will provide the formation of 8 × 12 = 96 molecules of ATP.
• for palmitic acid, the number of β-oxidation cycles is 7. In each cycle, 1 molecule of FADH 2 and 1 molecule of NADH are formed. Entering the respiratory chain, in total they “give” 5 ATP molecules. Thus, in 7 cycles 7 × 5 = 35 ATP molecules are formed.
• There are no double bonds in palmitic acid.
• 1 molecule of ATP is used to activate the fatty acid, which, however, is hydrolyzed to AMP, that is, 2 high-energy bonds or two ATP are spent.

Thus, summing up, we get 96 + 35-2 = 129 ATP molecules are formed during the oxidation of palmitic acid.